Research output per year
Research output per year
Johan L.Å. Nilsson, Anders Blomgren, Ulf J. Nilsson, Edward D. Högestätt, Lars Grundemar
Research output: Contribution to journal › Article › peer-review
Paracetamol overdosing may cause liver injury including fulminant liver failure due to generation of the toxic metabolites, N-acetyl-p-benzoquinone imine (NAPQI) and p-benzoquinone (p-BQ). Herein, the chelating agent, N,N'-Bis(2-mercaptoethyl)isophthalamide (NBMI), was examined for its potential ability to entrap NAPQI and p-BQ and to prevent paracetamol-induced liver injury. Both NBMI and the conventional paracetamol antidote N-acetylcysteine (NAC) were investigated with regard to their abilities to scavenge the NAPQI and p-BQ in a Transient Receptor Potential Ankyrin 1-dependent screening assay. Stoichiometric evaluations indicated that NBMI was able to entrap these metabolites more efficiently than NAC. Furthermore, oral administration of either NBMI (680 mg/kg) or NAC (680 mg/kg) prevented the development of the characteristic liver necrosis and elevation of serum alanine aminotransferase in a mouse model for paracetamol-induced liver injury. In summary, these results show that NBMI is able to entrap the toxic metabolites NAPQI and p-BQ and to prevent paracetamol-induced liver injury in mice.
Original language | English |
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Pages (from-to) | 589-593 |
Journal | Basic and Clinical Pharmacology and Toxicology |
Volume | 123 |
Issue number | 5 |
Early online date | 2018 Jun 16 |
DOIs | |
Publication status | Published - 2018 |
Research output: Thesis › Doctoral Thesis (compilation)